title: Calpain-10 interacts with plasma saturated fatty acid concentrations to influence insulin resistance in individuals with the metabolic syndrome.
abstract: BACKGROUND
  Calpain-10 protein (intracellular Ca(2+)-dependent cysteine protease) may play a role in glucose metabolism, pancreatic β cell function, and regulation of thermogenesis. Several CAPN10 polymorphic sites have been studied for their potential use as risk markers for type 2 diabetes and the metabolic syndrome (MetS). Fatty acids are key metabolic regulators that may interact with genetic factors and influence glucose metabolism.
  
  
  OBJECTIVE
  The objective was to examine whether the genetic variability at the CAPN10 gene locus is associated with the degree of insulin resistance and plasma fatty acid concentrations in subjects with MetS.
  
  
  METHODS
  The insulin sensitivity index, glucose effectiveness, insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)], insulin secretion (disposition index, acute insulin response, and HOMA of β cell function), plasma fatty acid composition, and 5 CAPN10 single nucleotide polymorphisms (SNPs) were determined in a cross-sectional analysis of 452 subjects with MetS participating in the LIPGENE dietary intervention cohort.
  
  
  RESULTS
  The rs2953171 SNP interacted with plasma total saturated fatty acid (SFA) concentrations, which were significantly associated with insulin sensitivity (P < 0.031 for fasting insulin, P < 0.028 for HOMA-IR, and P < 0.012 for glucose effectiveness). The G/G genotype was associated with lower fasting insulin concentrations, lower HOMA-IR, and higher glucose effectiveness in subjects with low SFA concentrations (below the median) than in subjects with the minor A allele (G/A and A/A). In contrast, subjects with the G/G allele with the highest SFA concentrations (above the median) had higher fasting insulin and HOMA-IR values and lower glucose effectiveness than did subjects with the A allele.
  
  
  CONCLUSIONS
  The rs2953171 polymorphism at the CAPN10 gene locus may influence insulin sensitivity by interacting with the plasma fatty acid composition in subjects with MetS. This trial was registered at clinicaltrials.gov as NCT00429195.
authors.affiliation: Lipid and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Cordoba, and CIBER Fisiopatologia Obesidad y Nutricion, Instituto de Salud Carlos III, Córdoba, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Perez-Martinez
authors.forename: Javier
authors.initials: J
authors.lastname: Delgado-Lista
authors.forename: Antonio
authors.initials: A
authors.lastname: Garcia-Rios
authors.forename: Jane F
authors.initials: JF
authors.lastname: Ferguson
authors.forename: Hanne L
authors.initials: HL
authors.lastname: Gulseth
authors.forename: Christine M
authors.initials: CM
authors.lastname: Williams
authors.forename: Brita
authors.initials: B
authors.lastname: Karlström
authors.forename: Beata
authors.initials: B
authors.lastname: Kieć-Wilk
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
authors.forename: Olfa
authors.initials: O
authors.lastname: Helal
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Małczewska-Malec
authors.forename: Catherine
authors.initials: C
authors.lastname: Defoort
authors.forename: Ulf
authors.initials: U
authors.lastname: Risérus
authors.forename: Wim H
authors.initials: WH
authors.lastname: Saris
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lovegrove
authors.forename: Christian A
authors.initials: CA
authors.lastname: Drevon
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Miranda
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D002154:Calpain / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005060:Europe; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D005227:Fatty Acids; D007328:Insulin; D002154:Calpain; C415197:calpain 10